Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming

BMC Genomics. 2018 Dec 22;19(1):956. doi: 10.1186/s12864-018-5326-1.

Abstract

Background: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse.

Results: To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human.

Conclusions: Our findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.

Keywords: Comparative epigenomics; Reprogramming; iPS cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Cellular Reprogramming / genetics*
  • Chromatin / metabolism*
  • Fibroblasts / cytology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Octamer Transcription Factor-3 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Species Specificity
  • Transcription Factors / metabolism*

Substances

  • Chromatin
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Transcription Factors